Generation of tissue resident CD8+ T cells during respiratory syncytial virus and influenza virus infection

Severe respiratory infections, especially in infants are the major cause of death worldwide. 50% of the total hospital admissions and 22% of hospitalizations in children are associated with respiratory viruses, most commonly the respiratory syncytial virus (RSV) and influenza A virus (IAV).

Currently, there are no vaccines available for RSV and limited cross-strain protection is induced by IAV vaccines. Recent reports show that lung resident memory T cells (TRM) play a central role in protecting from re-infection by respiratory viruses both in mice and humans. However, the mechanisms involved in the generation and maintenance of TRM cells are poorly defined. Preliminary data in my host lab using RSV-infected mice which lack the only receptor for type I Interferons show impaired CD8+ TRM responses. These data support the importance of a type I interferon response in the development of robust RSV-specific lung memory T cell immunity. We will use established mouse infection models of RSV and IAV, to investigate the mechanisms involved in the generation of optimal CD8+ TRM cells during RSV and IAV infection. Using human lung tissue, we will translate the findings and study functional responses of CD8+ TRM cells.

This project will help to increase our knowledge and understanding of the mechanisms underlying the generation of protective and long-lived anti-viral, lung resident T cells that are important for the memory responses to respiratory viral infections or after vaccination.